Sex differences in neurosteroid and hormonal responses to metyrapone in posttraumatic stress disorder
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- 作者：Sabra S. Inslicht (1) (2) (3)
Anne Richards (1) (2) (3)
Erin Madden (1) (2) (3)
Madhu N. Rao (1) (3) (4)
Aoife O’Donovan (1) (2) (3)
Lisa S. Talbot (1) (2) (3)
Evelyn Rucker (1) (2) (3)
Thomas J. Metzler (1) (2) (3)
Richard L. Hauger (5) (6)
Thomas C. Neylan (1) (2) (3) - 关键词：Sex differences ; Posttraumatic stress disorder ; Progesterone ; Allopregnanolone ; ACTH ; Metyrapone
- 刊名：Psychopharmacology
- 出版年：2014
- 出版时间：September 2014
- 年：2014
- 卷：231
- 期：17
- 页码：3581-3595
- 全文大小：514 KB
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Anne Richards (1) (2) (3)
Erin Madden (1) (2) (3)
Madhu N. Rao (1) (3) (4)
Aoife O’Donovan (1) (2) (3)
Lisa S. Talbot (1) (2) (3)
Evelyn Rucker (1) (2) (3)
Thomas J. Metzler (1) (2) (3)
Richard L. Hauger (5) (6)
Thomas C. Neylan (1) (2) (3)
1. Stress and Health Research Program, San Francisco VA Medical Center, 4150 Clement St. (116P), San Francisco, CA, 94121, USA
2. Department of Psychiatry, University of California, San Francisco, San Francisco, CA, 94143, USA
3. Northern California Institute for Research and Education (NCIRE), The Veterans Health Research Institute, San Francisco, CA, 94121, USA
4. Department of Medicine-Division of Endocrinology, University of California, San Francisco, San Francisco, CA, 94143, USA
5. Center of Excellence for Stress and Mental Health, San Diego VA Healthcare System, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA
6. Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA, 92093, USA - ISSN：1432-2072
文摘
Rationale Mechanisms contributing to sex differences in the regulation of acute stress responsivity and their effect on the increased incidence of posttraumatic stress disorder (PTSD) in women are poorly understood. The reproductive hormone, progesterone, through conversion to allopregnanolone (ALLO), suppresses the hypothalamic pituitary adrenal (HPA) axis and has potent anxiolytic effects. The potential that progesterone and allopregnanolone reactivity modulate HPA axis responses and account for sex differences in PTSD has not been previously examined. Objective The present study examined the effects of sex and PTSD on adrenocorticotropic hormone (ACTH), progesterone, and allopregnanolone responses to metyrapone and whether progesterone and allopregnanolone reactivity could affect the ACTH response in PTSD. Methods Healthy medication-free male and premenopausal follicular phase female participants with chronic PTSD (n--3; 49?% female) and controls (n--2; 50?% female) completed an overnight metyrapone challenge and ACTH, progesterone, and allopregnanolone were obtained by repeated blood sampling. Results The increase in ACTH response to metyrapone was higher in PTSD subjects compared to controls and in women compared to men. Contrary to our initial prediction of an inverse relationship, progesterone and allopregnanolone were positively associated with ACTH. Progesterone and allopregnanolone partially mediated the relationship between PTSD and ACTH. Conclusions Our findings of increased ACTH to metyrapone in PTSD and in women may reflect heightened hypothalamic CRF hypersecretion. Progesterone and allopregnanolone partially mediated the ACTH response in PTSD. Further characterizing sex differences in these processes will advance our understanding of the pathophysiology of PTSD, and may ultimately lead to better-targeted, more effective treatment.